引用本文:罗雀华,常 路,刘平平,舒海华.necrostatin-1鞘内注射抑制炎症反应减轻SNI大鼠神经病理性疼痛的实验观察[J].中国临床新医学,2020,13(5):495-499.
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necrostatin-1鞘内注射抑制炎症反应减轻SNI大鼠神经病理性疼痛的实验观察
罗雀华,常 路,刘平平,舒海华
510280 广州,南方医科大学第二临床医学院,广东省第二人民医院麻醉科
摘要:
[摘要] 目的 观察程序性坏死信号通路受体相互作用蛋白1/受体相互作用蛋白3[receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)]复合体通路抑制剂necrostatin-1(Nec-1)对外周神经病理性疼痛的影响。方法 将36只雄性SD大鼠随机分为空白对照组(Control组)、模型组(SNI组)和模型+给药组(Nec-1组),每组12只。Nec-1组和SNI组在SNI术后第5天分别经鞘内注射Nec-1(溶于二甲基亚砜)和等体积的二甲基亚砜,持续5 d;并于术前及术后第1、3、5、7、10、14天测定机械刺激缩足反射阈值(paw withdrawal mechanical threshold,PWMT)和热刺激缩足反应潜伏期(paw withdrawal thermal latency,PWTL)。术后第14天,麻醉后处死大鼠,在L4-L6段脊髓背角取材,应用Western blot法检测RIP1、RIP3、混合系激酶区域样蛋白(mixed-lineage kinase domain-like protein,MLKL)水平,ELISA检测促炎因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的表达水平。结果 与SNI组相比,Nec-1组第7、10、14天PWMT和PWTL均显著升高(P<0.05)。术后14 d,Nec-1组RIP1、RIP3、MLKL蛋白和促炎因子IL-1β、TNF-α、IL-6表达水平显著低于SNI组(P<0.05)。结论 Nec-1抑制脊髓背角细胞的坏死性凋亡能有效降低促炎因子水平并减轻神经病理性疼痛。
关键词:  Necrostatin-1  神经病理性疼痛  受体相互作用蛋白1/受体相互作用蛋白3  炎性因子
DOI:10.3969/j.issn.1674-3806.2020.05.16
分类号:R 614.4+1
基金项目:
Intrathecal injection of necrostatin-1 alleviates neuropathic pain in SNI rats via inhibiting inflammatory response
LUO Que-hua, CHANG Lu, LIU Ping-ping, et al.
The Second School of Clinical Medicine, Southern Medical University; Department of Anesthesiology, Guangdong Second Provincial General Hospital, Guangzhou 510280, China
Abstract:
[Abstract] Objective To investigate the effect of necrostatin-1(Nec-1), an inhibitor of receptor interacting protein-1/receptor interacting protein-3(RIP1/RIP3) signaling pathway, on peripheral neuropathic pain(NP). Methods Thirty-six male Sprague-Dawley SD rats were randomly divided into blank control group(control group), spared nerve injury group(SNI group) and the intrathecal necrostatin-1 group(Nec-1 group), with 12 cases in each group. Nec-1 and SNI groups were intrathecally injected with nec-1(dissolved in dimethyl sulfoxide) and the same volume of dimethyl sulfoxide on the day 5 for a consecutive 5 days after establishing the model of SNI. Paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency(PWTL) were measured preoperatively and on day 1, 3, 5, 7, 10 and 14 postoperatively. On the 14th day, the rats were anesthetized and sacrificed for spinal dorsal horn sampling in L4-L6 sections. The levels of RIP1, RIP3 and mixed-lineage kinase domain-like protein(MLKL) were detected by Western blot, and the expression levels of pro-inflammatory factors of interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were detected by enzyme-linked immunosorbent assay(ELISA). Results Compared with those in the SNI group, PWMT and PWTL in the Nec-1 group were significantly increased after intrathecal injection of necrostatin-1 on day 7, 10 and 14 postoperatively(P<0.05). Compared with those in the SNI group, the expressions of RIP1, RIP3 and MLKL proteins and the levels of IL-1β, TNF-α and IL-6 in the Nec-1 group were significantly reduced at the 14th day postoperatively(P<0.05). Conclusion The inhibition of Nec-1 on necroptosis of spinal dorsal horn cells can effectively alleviate neuropathic pain through reducing the level of pro-inflammatory factors.
Key words:  Necrostatin-1  Neuropathic pain(NP)  Receptor-interacting protein 1(RIP1)/Receptor-interacting protein 3(RIP3)  Inflammatory factors